The prostate gland is the site of two of the most frequent diseases that afflict elderly men: benign prostatic hyperplasia (BPH) and prostate cancer. The etiology of both diseases is thought to involve changes in prostate stem cells, the cells that are responsible for the growth and maintenance of the prostate gland. BPH and prostate cancer arise in different zones of the prostate. If the differences in stem cell biology between the different zones of the human prostate are elucidated, it may be possible to identify the factors regulating the major differences in susceptibility to prostate disease and design more effective means of controlling BPH and prostate cancer. The specific aims are to identify the epithelial stem cells in each zone of the human prostate and provide the resources for comparative analysis of gene and protein expression in stem cells of these different zones. The project will use normal human prostate tissue to (1) identify, isolate and characterize the epithelial stem cell population from each zone using flow sorting and lineage analysis, (2) to compare the patterns of differentiation between the zones using multiple immunostaining, and (3) to grow and store at least 3 large scale primary cultures of epithelial and mesenchymal cells derived from each zone for future analysis using DNA microarrays and proteomics. It is proposed that this project will lead to a greater understanding of why these two important diseases of elderly men develop in different parts of the prostate and provide the resources needed to develop new strategies for the prevention, management and therapy of BPH and prostate cancer.